Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression

被引：1941

作者：

Wray, Naomi R. ^{[1
,2
]}

Ripke, Stephan ^{[3
,4
,5
]}

Mattheisen, Manuel ^{[6
,7
,8
,9
]}

Trzaskowski, Maciej ^{[1
]}

Byrne, Enda M. ^{[1
]}

Abdellaoui, Abdel ^{[10
,11
]}

Adams, Mark J. ^{[12
]}

Agerbo, Esben ^{[8
,13
,14
]}

Air, Tracy M. ^{[15
]}

Andlauer, Till M. F. ^{[16
,17
]}

Bacanu, Silviu-Alin ^{[18
]}

Baekvad-Hansen, Marie ^{[8
,19
]}

Beekman, Aartjan F. T. ^{[20
,21
]}

Bigdeli, Tim B. ^{[18
,22
]}

Binder, Elisabeth B. ^{[16
,23
]}

Blackwood, Douglas R. H. ^{[12
]}

Bryois, Julien ^{[24
]}

Buttenschon, Henriette N. ^{[7
,8
,25
]}

Bybjerg-Grauholm, Jonas ^{[8
,19
]}

Cai, Na ^{[26
,27
]}

Castelao, Enrique ^{[28
]}

Christensen, Jane Hvarregaard ^{[6
,7
,25
]}

Clarke, Toni-Kim ^{[12
]}

Coleman, Jonathan I. R. ^{[29
]}

Colodro-Conde, Lucia ^{[30
]}

Couvy-Duchesne, Baptiste ^{[2
,31
]}

Craddock, Nick ^{[32
]}

Crawford, Gregory E. ^{[33
,34
]}

Crowley, Cheynna A. ^{[35
]}

Dashti, Hassan S. ^{[3
,36
]}

Davies, Gail ^{[37
]}

Deary, Ian J. ^{[37
]}

Degenhardt, Franziska ^{[38
,39
]}

Derks, Eske M. ^{[30
]}

Direk, Nese ^{[40
,41
]}

Dolan, Conor V. ^{[10
,11
]}

Dunn, Erin C. ^{[42
,43
,44
]}

Eley, Thalia C. ^{[29
]}

Eriksson, Nicholas ^{[45
]}

Escott-Price, Valentina ^{[46
]}

Kiadeh, Farnush Hassan Farhadi ^{[47
]}

Finucane, Hilary K. ^{[48
,49
]}

Forstner, Andreas J. ^{[38
,39
,50
,51
]}

Frank, Josef ^{[52
]}

Gaspar, Helena A. ^{[29
]}

Gill, Michael ^{[53
]}

Giusti-Rodriguez, Paola ^{[54
]}

Goes, Fernando S. ^{[55
]}

Gordon, Scott D. ^{[56
]}

Grove, Jakob ^{[6
,7
,8
,57
]}

机构：

[1] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia

[2] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

[3] Broad Inst, Med & Populat Genet, Cambridge, MA USA

[4] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[5] Univ Med Berlin, Campus Charite Mitte, Dept Psychiat & Psychothe, Berlin, Germany

[6] Aarhus Univ, Dept Biomed, Aarhus, Denmark

[7] Aarhus Univ, Ctr Integrat Sequencing, iSEQ, Aarhus, Denmark

[8] Lundbeck Fdn Initiat Integrat Psychiat Res, iPSYCH, Aarhus, Denmark

[9] Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden

[10] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands

[11] Vrije Univ Amsterdam, Inst Hlth & Care Res, EMGO+, Amsterdam, Netherlands

[12] Univ Edinburgh, Div Psychiat, Edinburgh, Midlothian, Scotland

[13] Aarhus Univ, Ctr Integrated Register Based Res, Aarhus, Denmark

[14] Aarhus Univ, Natl Ctr Register Based Res, Aarhus, Denmark

[15] Univ Adelaide, Discipline Psychiat, Adelaide, SA, Australia

[16] Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany

[17] Munich Cluster Syst Neurol SyNergy, Munich, Germany

[18] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA

[19] Statens Serum Inst, Dept Congenital Disorders, Ctr Neonatal Screening, Copenhagen, Denmark

[20] Vrije Univ, Med Ctr, Dept Psychiat, Amsterdam, Netherlands

[21] GGZ inGeest, Amsterdam, Netherlands

[22] Virginia Inst Psychiat & Behav Genet, Richmond, VA USA

[23] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA

[24] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[25] Aarhus Univ, Translat Neuropsychiat Unit, Dept Clin Med, Aarhus, Denmark

[26] European Bioinformat Inst EMBL EBI, Stat Genom & Syst Genet, Cambridge, England

[27] Wellcome Trust Sanger Inst, Human Genet, Cambridge, England

[28] Univ Hosp Lausanne, Dept Psychiat, Prilly, Switzerland

[29] Kings Coll London, MRC Social Genet & Dev Psychiat, London, England

[30] QIMR Berghofer Med Res Inst, Genet & Computat Biol, Herston, Qld, Australia

[31] Univ Queensland, Ctr Adv Imaging, Brisbane, Qld, Australia

[32] Cardiff Univ, Psychol Med, Cardiff, S Glam, Wales

[33] Duke Univ, Ctr Genom & Computat Biol, Durham, NC USA

[34] Duke Univ, Dept Pediat, Div Med Genet, Durham, NC 27706 USA

[35] Univ N Carolina, Biostat, Chapel Hill, NC USA

[36] Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA

[37] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland

[38] Univ Bonn, Inst Human Genet, Bonn, Germany

[39] Univ Bonn, Dept Gen, Life & Brain Ctr, Bonn, Germany

[40] Dokuz Eylul Univ, Sch Med, Psychiat, Izmir, Turkey

[41] Erasmus MC, Epidemiol, Rotterdam, Netherlands

[42] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA USA

[43] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA

[44] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit PNGU, Boston, MA 02114 USA

[45] 23andMe Inc, Res, Mountain View, CA USA

[46] Cardiff Univ, Neurosci & Mental Hlth, Cardiff, S Glam, Wales

[47] Univ British Columbia, Bioinformat, Vancouver, BC, Canada

[48] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[49] MIT, Dept Math, Cambridge, MA 02139 USA

[50] Univ Basel, Dept Psychiat UPK, Basel, Switzerland

来源：

NATURE GENETICS | 2018年 / 50卷 / 05期

基金：

美国国家卫生研究院; 欧洲研究理事会;

关键词：

LD SCORE REGRESSION; MENDELIAN RANDOMIZATION; SYSTEMATIC ANALYSIS; POLYGENIC RISK; LOCI; EPIDEMIOLOGY; METAANALYSIS; GWAS; INDIVIDUALS; DISORDERS;

D O I：

10.1038/s41588-018-0090-3

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.

引用

页码：668 / +

页数：16

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